From_a_Compound_to_a_Drug

=Board Game Content Analysis=

From Compound to Drug
This game is a race through the drug development process. Players will compete to get their compound made into an FDA drug. Their drugs will each need to go through the various stages of development including, from research and development, non-clinical testing, clincial studies, and manufacturing. Players will learn about the overall processes that all drugs must go through to prove their safety and quality before they can be approved by the FDA for use in humans as well as a basic understanding of the key players and regulations that control each step in the process.


 * ~ Content Type ||~ Content Elements ||~ Game Elements ||
 * ===Facts===
 * 1906 Federal Food and Drugs Act – prohibits interstate commerce in misbranded and adulterated drugs, drinks and food, administered by FDA (result of meat packing industry conditions, dangerous patient medicines)
 * 1938 Food, Drug and Cosmetic Act – (Elixir with antifreeze cause deaths of 107) – law required that safety be demonstrated, authorized inspections, outlawed false claims, required full list of ingredients and directions for safe use, FDA jurisdiction
 * 1988 Food and Drug Administration Act – established FDA as an agency
 * Applications requiring clinical data – user fees 2008 $11780000
 * FDA Performance Goal – Standard submission 90% in 10 months, priority 90% in 6 months; Class 1 (resubmission) – 90% in 2 months, priority 90% in 2 month; Class 2 (resubmission) – standard 90% in 6 month, priority “
 * GXP (collective laws of GCP, GLP and GMP)
 * Food and Drug Administration (FDA) – government agency that oversees the clinical, laboratory and manufacturing of drugs and biologics for human use
 * Average of 12 years for an experimental drug to go from a lab bench to be a manufactured drug (PhRMA Publication)
 * Clinical Hold - IND can be placed on Hold if FDA has concerns or issues regarding investigational new drug
 * Of the 5000-10000 drug components that ender Research and Development only 5 make it to the clinical trial state
 * Of the 5 compounds that enter clinical trial stage, one is approved for marketing
 * IND – Investigational new drug application
 * New Drug Application – includes administrative and prescribing information; document summaries, quality, non-clinical study reports
 * Safety- free from unexpected side effects
 * Identity - label states exactly what it is
 * Strength – delivers the correct dosage and potency over products life
 * Quality – Meets pre-established standards; performs as claimed; consistently produce the same product to meet the same specifications every time
 * Purity – free from physical, biological and chemical contamination
 * Applications Received/Approved in 2006 – 122, 80 approved
 * Master production and control record - document that describes the procedure for prep of a specific product
 * Batch production and control record- an exact copy of the approved MPCR issued for each production batch to record the data of the batch
 * Adulterated - Addition of toxic to food or other products for human consumption that alters the oringial form ||  || Message on Board

Message on board || ===The Food and Drug Administration (FDA) oversee the clincial, laboratory and manufacturing of drugs for humans in the U.S. They have jurisdiction over all U.S. pharmaceutical manufacturers and can audit, inspect and ensure companies follow laws and regulations.=== ===New products that are designed to treat human conditions or diseases are scrutinized by FDA's reviewers for safety and effectiveness before they can be made available to consumers. Companies that do not follow GXP Regulations and are caught by the FDA, can face serious consequences including being made to re-do studies, pay penalties, engage in corporate integrity agreements and go through increased FDA scrutiny in the forms of frequent audits and inspections.=== Personnel must be qualified to perform their jobs and have the education, experience and training to conduct their job - the FDA can issue a warning letter to the company to fix the situation if discoverd which may cause delays in the approvla process
 * ===Concepts===
 * Drug – chemically synthesized small molecules that are generally straightforward to manufacture (i.e. aspirin); regulated by FD&C Act, CDER, marketing application NDA, PDUFA Fees, Title 21 of the CFR; articles other than food intended to affect the structure or any function of the body of man or other animals
 * Biologics – biologically synthesized proteins that are generally thought to be more complex to manufacture in a consistent way; Public Health Services Act, CBER, Marketing application – BLA, subject to PDUFA Fees, Title 42 of US CFR; virus, serum, toxin, vaccine, allergenic product, etc. used to prevent or treat, cure a disease or condition in humans
 * FDA Guidance - documents that represent the FDA's current thinking on a particular subject, but are not binding legal requirements
 * Audits: An inspection or evaluation of a person, company, system, process, procudure or product, done internally or by the FDA to ensure the validity and reliabiltiy of the data and information. Audits reveal if the company is following the laws and regulations and ensures that data and processes are truthful and accurate.
 * GCP regulations – laws that govern clinical trials; governed by Title 21 CFR
 * GMP regulations – laws that govern manufacturing of all drug products for humans outlined in Title 21 CFR; state minimum standards for manufacturing, processing, packing and holding of drugs and finished pharmaceuticals (ensure safety, purity, identity, quality and strength of drugs); protect quality of manufactured products intended for human use
 * GLP regulations – laws that govern non-clinical studies; protect integrity of lab data that supports product applications; apply to non-clinical lab study (animal testing…)
 * IRBs – Institutional Review Boards composed of 5 members from various backgrounds
 * Adverse Event – any change in health or side-effect"that occurs in a person who participates in a clincial trial while the patient is receiving the treatment (study medication, application of the study device, etc.) or within a pre-specified period of time after their treatment has been completed.
 * Standard Operating Procedures - written standards or documentation that describes a routine procedure of general for how to perform a task, procedures that must be followed consistently and accurately
 * Drug product containers and closures – manufacturing phase, process – receipt, examine for defects, rejected, stored correctly ||  ||   ||
 * ===Principles===
 * GXP Regulations govern the U.S. drug development process related to laboratroy, clinical and manufacuturing practices. They are the minimum requirements to fulfill the law that must be followed in all activities related to GxP. If they are not followed, a company can be fined, products can be delayed in being approved or the company can be shut down.
 * Once an Investigational New Drug is submitted to the FDA, the company m ust wait 30 days before starting clinical trials
 * If your IND is placed on a Clinical Hold, you must postpone your Phase 1 Clinical study until the hold is removed If your IND is placed on a Clinical Hold, you must postpone your Phase 1 Clinical study until the hold is removed
 * All clinical study participants must be told the relevant information about the investigational drug that will be studied and give their written consent documenting their agreement that they were informed about the study
 * Clinical study participants may willingly drop out of a study at any time; if too many participants drop out; the study may need to be reconducted
 * If there are serious adverse events experienced during clinical studies, the studies must be put on hold and the IRB must review the data to decide whether the studies can continue or must be stopped
 * All laboratory and manufacturing documentation on batch production must be kept 2 years past the batch expiration date for FDA inspection
 * If something is not doucmented, it is considered not to have been done
 * Written procedures called Standard Operating Procedures outline many GxP processes and procedures and must be followed consistently and accurately by all employees to ensure the procedure is done the same way every time, producing the same results
 * If a drug is contaminated or made incorrectly, it could kill or harm a patient
 * During manufacturing testing, drug batches must be destroyed if a sample is found to be adulterated, contaminated or inpure
 * FDA Guidance – FDA’s current thinking on topic, not mandatory
 * Adequate safety margin to support starting dose and exposure during clinical trials
 * Identify specific safety issues and monitor during clinical trials
 * Must keep documentation at least 2 years past batch expiration date
 * Must have documentation available for audit
 * Drug containers can not be absorptive, additive or reactive
 * Equipment must not alter or contaminate the product
 * Logs must be kept on equipment use, cleaning, sanitizing, and calibration
 * Packaging and labeling must be controlled
 * Animals of different species must be housed in separate rooms when necessary animals of same species in different studies should be in separate spaces or have differentiation process and identification
 * Protocol must be followed in laboratory and clinical studies
 * Adequate filtration, ventilation, heat control in manufacturing plant; kept free from dust, etc.
 * Written procedures must be established for all processes and kept up to date
 * Ethical practices in clinical trials – IRB, financial disclosure, informed consent
 * Getting Informed consent – subject voluntarily confirms willingness to participate in trial; informed of all aspects of drug and potential effects, document; sign and date ||  ||   ||
 * ===Procedures===
 * Electronic Submission of IND to FDA – use software to compile data; validate systems; revalidate if need; computer security
 * Completing Phase 1 of clinical study – start 30 days after IND is submitted, obtain results; healthy volunteers or targeted disease populations (patients) to develop initial safety, tolerability, pharmacokinetics, dosing - > 50-100 people
 * Completing Phase 2 of clinical study– patients, short term measures of effectiveness, obtain additional safety information refine dosage; >100-300; during phase I must develop formulation manufacture phase II supplies, test and release for Phase II – start when I over, same in II
 * Performing Phase 3 of clinical trials- patients, long-term effectiveness, long-term safety, >1000 to 3000; get supplies from Phase II, get results, start assemble NDA materials, get results when submit – are groups ready to launch and manufacture
 * Getting Informed consent – subject voluntarily confirms willingness to participate in trial; informed of all aspects of drug and potential effects, document; sign and date
 * Submitting IND – summary non-clinical studies; clinical trial protocol – submit to FDA, FDA reviews, receive acknowledgement letter, 30-day review occurs; IND effective 30 days after receipt if no hold
 * Submission of NDA – submit to FDA, usually standard sometimes priority (products that meet unmet medical needs), different processes; review -
 * Post-Approval procedures– monitor AE, periodic safety updates to FDA, Phase 4 clinical trials to support safety; pediatrics studies; pregnancy registry; risk management
 * Submission of final report in non-clinical studies (lab) to FDA – contain all info, sign off by study director, QA ||  ||   ||
 * ===Processes===
 * Drug discovery – screen compounds for specific biological activities, target drug design, natural product screening, identification of deficient proteins/peptides in certain disease
 * Clinical study – must go through IRB, get informed consent, monitor; record data (paper or electronic), protocol, select investigators, monitors, train employees review data from studies, maintain IND, inform FDA of safety info., obtain IRB approval for study, get informed consent report adverse events to IRB, maintain case histories
 * Clinical Development – Phase 1, Phase 2, Phase 3 and Phase 4 sometimes; Pre-clinical testing and R&D: (1-3 years), phase 1,2,2 simultaneously occur, 2-10 years, NDA Review, approval (2months -7 years) – may be Phase 2a and 2b
 * Institutional Review Board – monitor safety of subjects, ensure protection of rights, safety and well being of subjects in trail, review and approval of protocols, amendments, methods, documentation, informed consent
 * Quality Assurance – check written procedures, reviewing production records, ensure errors are investigated; approve and reject manufactured drugs; internal audit
 * Research and development – Discovery – put together CMC assessment, assemble IND< understand initial research data on candidate, generate data about and characteristics, do risk assessment, preliminary formulation screen; 6-9 months
 * Preclinical – 9-15 months, prepare IND materials, get materials for clinical ready, develop Phase I formulation, determine method delivery, write IND, test and release clinical supplies for Phase II, test formational for development supplies.
 * Clinical phases for development: 4 phases ; phase 1 test on small groups to determine safety and pharmacological data; 2 – once initial safety determined – trials test who suffer from condition may be divided into two phases IIA determine dosing and IIB to determine efficacy – some combine into one and monitor toxicity and efficacy together (if successful – sponsor may move forward)l phase III randomized, controlled and larger population company efficacy of the new therapy with existing therapy; can be divide into 2 parts IIIA – pre-clinical, pharmacologic, efficacy, safety data, labeling, packaging production plans and IIIB – when IIIA is pending review and may demonstrate effeminacy for additional uses, supplemental safety data and support marketing claims; phase IV – post launch safety surveillance to detect long term effects
 * Manufacture process – lab tests to prove safety – lab controls – each drug product must be testes to determine conformity with specifications; it can be reproduced (stability, contamination_
 * Lab (non-clinical)– study director (overall technical conduct of study is within responsibility), QA Unit; facility suitable size (animal care and supply facility; lab operation areas specimen controls and data storage) – test and control articles must be recorded, stored properly, follow protocol and report accurately ||  ||   ||
 * ===Probabilities===
 * Equipment fails or malfunctions
 * Surprise audit by FDA
 * Clinical Hold on IND application – must wait to start Phase I of Clinical Trials
 * Consequence not following regulations– prosecution, seizure of product, injunction, warning letter from FDA, consent decree, fines, recall
 * Adverse events experienced during clinical study – IRB must be contacted and decide if study should proceed
 * Injured subject alleges inadequately informed of risks
 * Subject accuses sponsor of continuing investigation with unreasonable significant risk
 * FDA requires minimum requirements is not an an adequate defense
 * Rouge employee; employees aren’t properly trained
 * Drug product contaminated, altered
 * Data reported inaccurately or dishonestly
 * People drop out of study
 * Change in protocol – back through IRB
 * Study director quits
 * Funding
 * Competitors drugs
 * Initial study data – may be insignificant ||  ||   ||
 * ===Context===
 * Lab for R&D, board moves to Non-clinical study with animals and lab, Clinical Study Phase, has different doctors clinics, office settings, Manufacture phase moves into manufacturing plant
 * Context is the overall physical locations where each process occurs ||  ||   ||
 * ===Vantage Points===
 * Adults, new to pharmaceutical industry - new hires who are entering the company and know little about the entire drug devlopment process - need a g eneral understanding of what a drug goes through before it is marketed so they can understand how they fit into the overall process
 * Different roles could include - management, line workers in manufacturing; study directors; study monitor; quality assurance user; C.E.O.; regular employee; Sales force; lab analyst; Regulatory Affairs; someone who works in lab, clinical or manufacturing area; patients ||  ||   ||